The cephalic phase insulin secretion has been characterized and quantified using the non metabolized sweetener, saccharin, in anesthetized, freely moving rats. Cephalic phase insulin secretion required an intact innervation of the pancreas. The proposed work in this area will be to determine the possible importance of this type of insulin secretion in experimental (e.g. dietary) and genetic obesities. The gustatory afferences (that initiate cephalic phase insulin secretion) from the oral cavity to the brain stem and diencephalon have been studied electrophysiologically in anesthetized rats. Chorda tympani stimulation (CT) elicited increased firing rates of several neurons of the nucleus of the solitary tract (NTS). Futhermore, stimulation of lateral hypothalamus (not that of more medial sites) inhibited the increased firing rate, due to chorda tympani stimulation, in CT-sensitive neurons, suggesting a modulation of NTS neurons by lateral hypothalamus. Such modulation, and the characterization of the efferent pathways implicated in cephalic phase insulin secretion, will be further investigated using analogous methodology. Lesions in the ventromedial hypothalamus A (VMH) produced (hyperphagia being prevented) alterations of the secretory activity in subsequently isolated and perfused pancreases (i.e., 7 days after VMH lesions). These alterations were: a) increased insulin secretion; b) increased glucagon secretion; c) decreaded somatostatin secretion. The possible role of the vagus nerve and of humoral factor(s) in bringing about these changes will be studied, and extended to the study of genetic obese animals.